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SARS-Co-V-2 Sequencing Studies Elucidate Intrahost Diversity, Spread of New Lineage

NEW YORK — While most SARS-CoV-2 infections have low within-host diversity and limited variant transmission, if variants are transmitted, they could spread quickly, a new study has found. Another new study, meanwhile, recounted how quickly a new viral variant may become common.

As the COVID-19 pandemic has raged on, genomic surveillance methods have enabled researchers to track the emergence and spread of new SARS-CoV-2 viral lineages. Currently, viral variants of concern include the B.1.1.7 lineage, which is suspected to have an increased transmission ability, and the B1.351 and P.1 lineages, which may escape vaccine-acquired or previous infection-induced immunity.

One study appearing today in Science examined how frequently new variants arise within infected individuals, while another appearing in Nature explored how some variants like the B1.351 lineage may then spread through the wider population. Studying the rise and spread of SARS-CoV-2 could help inform pandemic response, and underscore the need for continued and coordinated global genomic surveillance of SARS-CoV-2.

By deeply sequencing SARS-CoV-2 samples from the UK, researchers led by the University of Oxford's Tanya Golubchik found that most viral infections had low within-host diversity, as they reported in Science.

They analyzed 1,390 SARS-CoV-2 genomes collected via nasopharyngeal swabs from 1,173 different individuals at two hospital sites between March and June 2020. For 41 individuals, they collected multiple samples at different time points.

Overall, they found low levels of intrahost viral diversity in samples with high viral load. Still, they noted that within-host variants did arise in most samples, including ones affecting the gene encoding the spike protein.

As some of the sampled individuals were members of the same household, the researchers found that a portion of the within-host variants could be transmitted. However, they reported that transmission represents a narrow bottleneck, as most — though not all — variants are lost at that point.

These findings suggested to the researchers that while variants that are better at being transmitted or better at avoiding immune responses may crop up infrequently, they could, if transmitted successfully, spread quickly.

One variant that has spread quickly is B1.351, which is also known as 501Y.V2. Researchers led by the University of KwaZulu-Natal's Tulio de Oliveira reported in Nature today their identification of the 501Y.V2 lineage in South Africa.

The researchers analyzed 2,882 SARS-CoV-2 genomes collected in South Africa between early March and mid-December 2020. Through this, they identified a new monophyletic cluster of 341 sequences from samples collected between October and December, when a second epidemic wave roiled South Africa. This cluster, they noted, was phylogenetically distinct from the three main lineages circulating there and, by mid-November, the 501Y.V2 lineage became dominant in three provinces.

According to the researchers, this lineage is marked by hypermutation along both the whole genome and affecting the spike protein gene region, including nonsynonymous alterations leading to amino acid changes in the spike protein. They added that preliminary studies have suggested that 501Y.V2 could be 50 percent more transmissible than variants circulating previously. Further, some limited data has indicated that 501Y.V2 exhibits some or complete escape from neutralizing antibodies in convalescent plasma, suggesting reinfection may be possible.

As 501Y.V2 has a high number of mutations, de Oliveira and his colleagues noted that one theory posits that it arose through intra-host evolution.

"Whilst the full implications of this new lineage in South Africa are yet to be determined, these findings highlight the importance of coordinated molecular surveillance systems in all parts of the world, to enable early detection and characterization of new lineages and to inform the global pandemic response," de Oliveira and his colleagues wrote in their paper.